Absence of pregnancy-induced alterations in tissue insulin sensitivity in the offspring of diabetic rats

1991 ◽  
Vol 131 (3) ◽  
pp. 387-393 ◽  
Author(s):  
K. Holemans ◽  
L. Aerts ◽  
F. A. Van Assche
Keyword(s):  
Insulin Resistance ◽  
Gestational Diabetes ◽  
Normal Pregnancy ◽  
Diabetic Rats ◽  
Metabolic Clearance ◽  
Response Curves ◽  
Pregnant Rats ◽  
Peripheral Tissues ◽  
Glucose Levels ◽  
Peripheral Insulin Resistance

ABSTRACT We have previously demonstrated insulin resistance in the liver and peripheral tissues of the adult offspring of rats made diabetic with streptozotocin (SDF rats). In this study, a euglycaemic hyperinsulinaemic clamp was used to test the hypothesis that insulin resistance is further aggravated during pregnancy in SDF rats. Normal pregnancy was accompanied by a decrease in the sensitivity of the liver and peripheral tissues to insulin, with a normal responsiveness to insulin. In SDF rats no further decrease in the sensitivity of peripheral tissues to insulin occurred during pregnancy when compared with non-pregnant rats, and the dose–response curves of the glucose metabolic clearance rate during hyperinsulinaemia were similar in pregnant control and pregnant SDF rats. There was, however, a modest decrease in the sensitivity of the liver to insulin during pregnancy in SDF rats. The normal increase in plasma insulin levels during pregnancy was blunted in SDF rats: this resulted in increased glucose levels in maternal and fetal rats and increased fetal insulin concentrations, features compatible with mild 'gestational diabetes'. In conclusion, gestational diabetes develops in pregnant SDF rats, although there is no further deterioration in peripheral insulin resistance. Journal of Endocrinology (1991) 131, 387–393

Cellular Mechanisms for Insulin Resistance in Normal Pregnancy and Gestational Diabetes

Diabetes Care ◽  
2007 ◽  
Vol 30 (Supplement 2) ◽  
pp. S112-S119 ◽  
Author(s):  
L. A. Barbour ◽  
C. E. McCurdy ◽  
T. L. Hernandez ◽  
J. P. Kirwan ◽  
P. M. Catalano ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gestational Diabetes ◽  
Normal Pregnancy ◽  
Cellular Mechanisms

scholarly journals Programming of growth, insulin resistance and vascular dysfunction in offspring of late gestation diabetic rats

2009 ◽  
Vol 117 (3) ◽  
pp. 129-138 ◽  
Author(s):  
Emily M. Segar ◽  
Andrew W. Norris ◽  
Jian-Rong Yao ◽  
Shanming Hu ◽  
Stacia L. Koppenhafer ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Diabetic Rats ◽  
Late Gestation ◽  
Group Differences ◽  
Pregnant Rats ◽  
Increased Risk ◽  
Specific Insulin ◽  
Diabetic Mothers

ODM (offspring of diabetic mothers) have an increased risk of developing metabolic and cardiovascular dysfunction; however, few studies have focused on the susceptibility to disease in offspring of mothers developing diabetes during pregnancy. We developed an animal model of late gestation diabetic pregnancy and characterized metabolic and vascular function in the offspring. Diabetes was induced by streptozotocin (50 mg/kg of body weight, intraperitoneally) in pregnant rats on gestational day 13 and was partially controlled by twice-daily injections of insulin. At 2 months of age, ODM had slightly better glucose tolerance than controls (P<0.05); however, by 6 months of age this trend had reversed. A euglycaemic–hyperinsulinamic clamp revealed insulin resistance in male ODM (P<0.05). In 6–8-month-old female ODM, aortas had significantly enhanced contractility in response to KCl, ET-1 (endothelin-1) and NA (noradrenaline). No differences in responses to ET-1 and NA were apparent with co-administration of L-NNA (NG-nitro-L-arginine). Relaxation in response to ACh (acetylcholine), but not SNP (sodium nitroprusside), was significantly impaired in female ODM. In contrast, males had no between-group differences in response to vasoconstrictors, whereas relaxation to SNP and ACh was greater in ODM compared with control animals. Thus the development of diabetes during pregnancy programmes gender-specific insulin resistance and vascular dysfunction in adult offspring.

scholarly journals Gestational diabetes mellitus causes dyslipidemia in late trimester: mini review

2019 ◽  
Vol 9 (1) ◽  
pp. 453
Author(s):  
Poonguzhalai S. ◽  
Kalyanikutty K. P.
Keyword(s):  
Diabetes Mellitus ◽  
Lipid Metabolism ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Gestational Age ◽  
Significant Risk ◽  
Normal Pregnancy ◽  
Adverse Outcomes ◽  
Peripheral Tissues ◽  
Management Protocol

The incidence of gestational diabetes mellitus (GDM) is increasing rapidly worldwide. Many women with gestational diabetes mellitus are likely to have type 2 diabetes. With the extensive management protocol for GDM we are able to obtain a good glycaemic control but still excess morbidity prevails among GDM pregnancy compared to normal pregnancy. This may be due to the dysfunction of lipid metabolism. Changes in carbohydrate and lipid metabolism occur during pregnancy to ensure a continuous supply of nutrients to the growing fetus despite intermittent maternal food intake. Exaggerated reduction in insulin sensitivity in the peripheral tissues combined with peripheral adipose tissue lipolysis in GDM pregnancy than normal pregnancy results in increased maternal lipoprotein concentrations and elevated lipoprotein triglyceride content. An altered lipid profile on the maternal side would modulate the quantity and quality of lipids being transferred to the fetus. Hypertriacylglycerolemia in gestational diabetes mellitus has been related to a significant risk of having neonates that are large for gestational age and it is considered as a major cause of preeclampsia in the late gestational age. So, the recent researchers emphasize on targeting lipid metabolism in pregnant women with GDM to avoid the adverse outcomes of pregnancy.

scholarly journals Beneficial effects of walnut (Juglans regia L.) oil-derived polyunsaturated fatty acid prevents a prooxidant status and hyperlipidemia in pregnant rats with diabetes

2020 ◽  
Author(s):  
Bingmei Sun ◽  
Hua Yan ◽  
Chao Li ◽  
Linlin Yin ◽  
Fei Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Fatty Acid ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Juglans Regia ◽  
Diabetic Rats ◽  
Pregnant Rats ◽  
Beneficial Effects ◽  
Pregnant Diabetic

Abstract Background: Gestational diabetes mellitus has a long-term effect on pregnant women. Walnut (Juglans regia L.) oil-derived polyunsaturated fatty acid (PUFA) possesses multifarious pharmacological activities. This study investigated the beneficial effects of walnut oil-derived PUFA on glucose metabolism, pregnancy outcomes, oxidative stress, and lipid metabolism in gestational diabetes mellitus.Methods: The GDM rat model was generated by intraperitoneal injection of streptozotocin (40 mg/kg) on gestational day (GD) 6, GD7 and GD8. The differences between groups were estimated using one-way ANOVA followed by the Tukey’s multiple comparison test for post-hoc analysis.Results: The results indicated that PUFA could mitigate GDM in pregnant diabetic rats, as embodied by the decrease of fasting blood glucose and the increase of plasma insulin and hepatic glycogen levels. Also, PUFA could suppress oxidative stress in pregnant diabetic rats, as reflected by the decrease of malondialdehyde (MDA) content, an increase of superoxide dismutase (SOD), catalase (CAT) and gutathione peroxidase (GSH-Px) activities. PUFA could also mitigate the abnormal changes of lipid profiles in plasma and hepatic tissue. Moreover, the relative mRNA expression of sterol regulatory element-binding transcription factor-1 (SREBP-1), stearoyl-CoA desaturase-1 (SCD-1), fatty acid synthase (FAS), and acetyl-coenzyme A carboxylase (ACC), was suppressed by PUFA in pregnant diabetic rats.Conclusions: These results suggested that PUFA supplementation during pregnancy is beneficial in preventing diabetic complications in pregnant rats.

Temporal changes in insulin resistance and secretion in 24-h-fasted conscious pregnant rats

1993 ◽  
Vol 265 (6) ◽  
pp. E845-E851 ◽  
Author(s):  
G. Rossi ◽  
R. S. Sherwin ◽  
A. S. Penzias ◽  
P. Lapaczewski ◽  
R. J. Jacob ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Action ◽  
Insulin Dose ◽  
Glucose Production ◽  
Late Pregnancy ◽  
Hepatic Insulin Resistance ◽  
Pregnant Rats ◽  
Hyperglycemic Clamp ◽  
Peripheral Insulin Resistance ◽  
Insulin Responses

To determine the temporal sequence of pregnancy-induced changes in insulin action and secretion, awake midpregnant (11-12 days) and late pregnant (19-20 days) rats underwent a two-step euglycemic hyperinsulinemic or a hyperglycemic clamp study after a 24-h fast. During euglycemia, insulin-stimulated increments in glucose uptake and clearance in midpregnant rats were reduced by 60-70% at the lower dose (insulin approximately 360 pM) and by 20-30% at the higher dose (insulin approximately 1,750 pM; P < 0.01 vs. virgin controls). Insulin action was also diminished in late pregnant rats. However, the magnitude of resistance did not increase. Insulin-mediated suppression of glucose production was only minimally impaired in midpregnancy. In contrast, glucose production was virtually unchanged in late pregnancy, even at the highest insulin dose. During hyperglycemia, insulin responses in late pregnancy were markedly increased 5-fold above controls and 2.5-fold above midpregnant rats (P < 0.05). We conclude that rat pregnancy is characterized by the early appearance of peripheral insulin resistance. As pregnancy progresses toward term, marked hepatic insulin resistance and insulin hypersecretion develop, whereas peripheral insulin resistance demonstrates negligible changes. These data imply that insulin hypersecretion during late pregnancy is most closely linked to hepatic insulin resistance, at least in 24-h-fasted animals.

scholarly journals Correlation of maternal serum fetuin/alpha2-HS-glycoprotein concentration with maternal insulin resistance and anthropometric parameters of neonates in normal pregnancy and gestational diabetes

2002 ◽  
pp. 243-248 ◽  
Author(s):  
L Kalabay ◽  
K Cseh ◽  
A Pajor ◽  
E Baranyi ◽  
GM Csakany ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gestational Diabetes ◽  
Pregnant Women ◽  
Normal Pregnancy ◽  
Tnf Alpha ◽  
Control Group ◽  
Anthropometric Parameters ◽  
Necrosis Factor Alpha ◽  
C Peptide ◽  
Glucose Ratio

OBJECTIVE: Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. DESIGN: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns. CONCLUSION: AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.

scholarly journals Molecular mechanisms of insulin resistance in normal pregnancy and gestational diabetes

2021 ◽  
Vol 2021 (1) ◽  
pp. 22-30
Author(s):  
L.V. Zhuravlyova ◽  
◽  
N.V. Sokolnikova ◽  
T.A. Rogachova ◽  
◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gestational Diabetes ◽  
Molecular Mechanisms ◽  
Normal Pregnancy ◽  
Inflammatory Factors ◽  
Ppar Γ ◽  
Tnf Α ◽  
Therapeutic Measures ◽  
Glut 4 Translocation ◽  
Further Development

The purpose of this review article is to analyze current information on the molecular mechanisms of gestational diabetes and the prospects for their use in the further development of new effective treatments for this common pathology. Decreased ability of insulin to bind to its receptor, decreased IRS-1 expression and GLUT-4 translocation, and increased levels of p85α-PI-3 kinase subunits are involved in the development of insulin resistance during pregnancy. In gestational diabetes, there are not only more significant changes of the above mentioned indicators, but also increased levels of pro-inflammatory factors: TNF-α, IL-6, leptin and decreased insulin-sensitizing factors: adiponectin and PPAR-γ. Therapeutic measures aimed at normalizing the secretion of cytokines and adipokines reduce the risk of gestational diabetes mellitus and its complications and require further development

scholarly journals Some mechanisms of inflammation development in type 2 diabetes mellitus

2021 ◽  
Vol 24 (4) ◽  
pp. 334-341
Author(s):  
L. A. Bochkareva ◽  
L. V. Nedosugova ◽  
N. A. Petunina ◽  
M. Е. Теlnova ◽  
E. V. Goncharova
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Intracellular Signaling ◽  
Peripheral Tissues ◽  
Surface Receptors ◽  
Peripheral Insulin Resistance ◽  
Systemic Insulin Resistance ◽  
M1 Polarization ◽  
Anti Inflammatory

Inflammation plays a key role in the development and progression of type 2 diabetes (T2DM), a disease characterized by peripheral insulin resistance and systemic glucolipotoxicity. The main source of inflammation in the early stages of the disease is visceral adipose tissue (VT). Macrophages are innate immune cells that are present in all peripheral tissues, including VT. Violation of the response of VT (MT) macrophages to changes in the microenvironment underlies aberrant inflammation and the development of local and systemic insulin resistance. The inflammatory activation of macrophages is regulated at several levels: stimulation of cell surface receptors, intracellular signaling, transcription, and metabolic levels. Which are activated by the transformation of macrophages along the pro-inflammatory or anti-inflammatory pathways. Such polarization of macrophages in modern immunology is divided into classical anti-inflammatory M1 polarization and alternative anti-inflammatory M2 polarization of macrophages. The M1 / M2 ratio of macrophages in the process of inflammation ensures the resolution of inflammation at different stages of its development. The review considers the main mechanisms involved in VT inflammation and the development of insulin resistance in T2DM, supported with the participation of immunocompetent cells, M1 / M2, as well as growth factors and humoral immunity factors secreted during this process.

scholarly journals Magnesium upregulates insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide-induced type-2 diabetic rats

2018 ◽  
Vol 52 (1) ◽  
pp. 6-16 ◽  
Author(s):  
Ayodele Olufemi Morakinyo ◽  
Titilola Aderonke Samuel ◽  
Daniel Abiodun Adekunbi
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Transporter ◽  
Diabetic Rats ◽  
Glucose Transporter 4 ◽  
Magnesium Supplementation ◽  
Glucose Levels ◽  
Type 2 Diabetic

Abstract Objective. We investigated the effects of magnesium supplementation on glucose tolerance, insulin sensitivity, oxidative stress as well as the concentration of insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide induced type-2 diabetic (T2D) rats. Methods. Rats were divided into four groups designated as: 1) control (CTR); 2) diabetic untreated (DU); 3) diabetic treated with 1 mg of Mg/kg diet (Mg1-D); and 4) diabetic treated with 2 mg of Mg/kg diet (Mg2-D). T2D was induced with a single intraperitoneal (i.p.) injection of freshly prepared streptozotocin (55 mg/kg) aft er an initial i.p. injection of nicotinamide (120 mg/kg). Glucose tolerance, insulin sensitivity, lipid profile, malondialdehyde (MAD) and glutathione content, insulin receptors (INSR) and glucose transporter-4 (GLUT4), fasting insulin and glucose levels were measured, and insulin resistance index was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR). Results. Magnesium supplementation improved glucose tolerance and lowered blood glucose levels almost to the normal range. We also recorded a noticeable increase in insulin sensitivity in Mg-D groups when compared with DU rats. Lipid perturbations associated T2D were significantly attenuated by magnesium supplementation. Fasting glucose level was comparable to control values in the Mg-D groups while the HOMA-IR index was significantly lower compared with the DU rats. Magnesium reduced MDA but increased glutathione concentrations compared with DU group. Moreover, INSR and GLUT4 levels were elevated following magnesium supplementation in T2D rats. Conclusion. These findings demonstrate that magnesium may mediate effective metabolic control by stimulating the antioxidant defense, and increased levels of INSR and GLUT4 in diabetic rats.

Abstract 206: Hyperleptinemia Increases Blood Pressure and Decreases Pup Weight in Pregnant Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ana C Palei ◽  
Eric M George ◽  
Marietta Arany ◽  
Kathy Cockrell ◽  
Joey P Granger
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Normal Pregnancy ◽  
Developed Countries ◽  
Late Gestation ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Glucose Levels ◽  
Sprague Dawley Rats ◽  
Relationship Of

While the relationship of obesity to cardiovascular disease is well recognized, it also has important implications for pregnancy outcomes. Indeed, there is compelling evidence that obesity increases the risk of preeclampsia (PE). The risk of severe and mild PE and PE occurring in early and late gestation are greater in obese and overweight women. Despite the fact that obesity is the leading attributable risk for PE in developed countries, the pathophysiological mechanisms whereby obesity and metabolic factors such as leptin increases the risk for developing PE are unclear. Hyperleptinemia over the levels seen in normal pregnancy has been associated with preeclampsia. Thus the aim of this study was to investigate whether chronic hyperleptinemia causes changes in cardiovascular, metabolic and reproductive systems of pregnant rats. On gestational day (GD) 14, Sprague Dawley rats were assigned to normal pregnant (NP, n=8) group or to NP plus Leptin group (NP+Lep, n=8), in which miniosmotic pump with leptin (0.5 μg/kg/min) was placed intraperitoneally. On GD 19, mean arterial pressure (MAP) was recorded, rats were sacrificed, and blood, placentas and pups were collected. Body weight (BW) and food intake (FI) were measured on GD 16-18. Serum leptin concentration was elevated in NP+Lep compared with NP (0.82 ± 0.05 vs 17.98 ± 2.75 ng/mL, P<0.05). Circulating insulin and glucose levels were similar in NP and NP+Lep groups (both P>0.05). MAP was higher in NP+Lep compared with NP (102.40 ± 2.38 vs 121.30 ± 8.13 mmHg, P<0.05). BW was decreased in NP+Lep compared with NP at GD 19 (330.90 ± 9.08 vs 284.10 ± 8.58 g, P<0.05), probably due to the reduced FI of the NP+Ins group compared with NP during GD 16-18 (23.45 ± 0.61 vs 8.61 ± 0.83 g/day, P<0.05). Although the number of viable fetuses per rat was similar between groups (P>0.05), fetuses and placentas of the NP+Lep group were lighter than those of the NP group (2.29 ± 0.06 vs 2.11 ± 0.06 g and 0.58 ± 0.01 vs 0.50 ± 0.02 g, respectively, both P<0.05). In conclusion, leptin increases blood pressure, despite its effect of reducing body weight during pregnancy, representing a possible mechanism to induce hypertension in preeclampsia. In addition, leptin decreases pup and placental weights, which could lead to abnormal fetal outcomes.

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